Angiogenesis, formation of new blood vessels, occurs in the healthy body for healing wounds and restoring blood flow to tissues after injury. The angiogenic process is tightly controlled by various positive and negative regulatory factors. In many disease states, the body loses control over angiogenesis.
Excessive blood vessel growth may be triggered by certain pathological conditions such as cancer, age-related macular degeneration, rheumatoid arthritis, and psoriasis. As a result of excessive angiogenesis, new blood vessels feed diseased tissues and destroy normal tissues. In cancer, the new vessels allow tumor cells to escape into the circulation and lodge in other organs.
Angiogenesis occurs via a series of sequential steps, including division and migration of endothelial cells that form the walls of blood vessels. About 15 proteins are known to activate endothelial cell growth and movement. Therefore, angiogenesis can be suppressed by inhibitors of these activating proteins, e.g., angiogenin, epidermal growth factor, estrogen, fibroblast growth factor, interleukin 8, prostaglandins E1 and E2, tumor necrosis factor, vascular endothelial growth factor, or granulocyte colony-stimulating factor.
Excessive angiogenesis-related disorders include cancer (both solid and hematologic tumors), cardiovascular diseases (e.g., atherosclerosis), chronic inflammation (e.g., rheutatoid arthritis or Crohn's disease), diabetes (e.g., diabetic retinopathy), psoriasis, endometriosis, and adiposity. See, e.g., Pharmacological Reviews 52: 237–268, 2001. Compounds that effectively inhibit angiogenesis are drug candidates for treating or preventing these disorders.